This proposal seeks to identify the cellular origin, distribution and functional properties of the endogenous morphine-like peptides (endorphins). Cellular level studies on rat, mouse and squirrel monkey central nervous systems will determine the participation of the peptide-producing cells in synaptic transmission and in noci-ception, analgesia, euphoria, and general behavior. Using immunocytochemical techniques with antibodies prepared against alpha endorphin (beta LPH 61-79), against beta endorphin (beta LPH 61-91) and beta LPH, cells and cell processes containing these peptides will be located and related to other cytochemically-reactive and functionally discernible neuronal systems. Using electrophysiological methods (extracellular unit recording, microiontophoretic administration, and electrical activation of selected pathways to identifiable target neurons), the endorphins, their synthetic analogs, and other opioid peptides will be evaluated for selectivity and similarity of action on discharge rate, pattern, and interaction with pathways of known transmitter mediation. Cell systems tested will be selected by immunocytochemical data, by reported ability to bind opiate agonists or antagonists with high affinity or by participation in noci-ceptive somesthestic or other pathways. Studies will also be carried out after development of morphine-dependence and acutely after withdrawal. These experimental studies can provide a definitive characterization of the sites, mechanisms, and functional properties of cells which release or respond to the endorphins and the general function of these systems in brain function and behavior. These data may help both to develop non-addicting analgesics and to further the fundamental mental understanding of cellular functioning of the brain and the nature of cellular mechanisms involved in drug abuse.